The primary goal of the project is to determine the mechanisms of action of several of the most extensively used anti-tuberculosis drugs, including isoniazid, rifampin, ethionamide, ethambutol, pyrazinamide, and the clinically useful aminoglycosidic antibiotics (streptomycin, kanamycin, viomycin, and capreomycin). The means by which mycobacteria develop drug-resistance are also pertinent to the project. In addition, experiments are planned which will investigate the anti- mycobacterial effects of drug combinations with the goal of finding drug regimens which are synergistic in relationship. The methods of study usually include measurements of drug effects on the incorporation of specific metabolic precursors into essential cellular components in Mycobacterium bovis strain BCG, avirulent strains of Mycobacterium tuberculosis, or various atypical mycobacterial strains. BIBLIOGRAPHIC REFERENCES: McLatchy, J. K. et al. 1976. Cross-resistance between aminoglycoside antimicrobial drugs and its influence on the retreatment chemotherapy of tuberculosis. Amer. Rev. Resp. Dis. McClathy, J. K. 1976. Mycobacterium szulgai. Check Sample Program, Amer. Soc. Clin. Pathol. (in press).